Nicotine [1-methy1-2-(3-pyridyl) pyrrolidine ] 
In man, nicotine is metabolized.to cotinine, hydroxycotinine, desmethyl- 
cotinine, and other unidentified compounds (148, 149). In other studies with 
c!4_1abeled nicotine, the nicotine isomethonium ion was isolated: from urine 
after intravenous administration (956). 
After administration of nicotine to dogs, both orally and intravenously, 
urine was collected and analyzed. There was no prolonged storage of nicotine 
since about 95% appeared in the urine after 36 hours (106). A number of com- 
pounds were isolated from the urine and identified: (-) cotinine (III), (-) 
desmethylcotinine (V), hydroxycotinine (VI), Y-methylamino-Y-(2-pyridy1) 
butyric acid (II), B-oxo-Y-(3-pyridy1)-N-methylbutyramide (IV), 3-pyridylacetic 
acid (VII). A variety of other compounds resulted from demethylation of 
cotinine and production of one-carbon metabolites and from the loss of two 
labeled carbons in the pyrrolidine ring. Tests also showed that V spontane- 
ously cyclized to the lactam (IID at physiological pH (854, 953, 954, 955, 
956, 958). The nicotine isomethonium ion was also found in urine of dogs to 
whom nicotine had been administered (1431). 
After administration of cotinine to dogs, (-) desmethylcotinine (V), 
hydroxycotinine (VI) and a compound thought to be butyramide (IV) were iso- 
lated from urine (952, 957). 
In vitro studies with rabbit liver microsomes, TPNH, and 02, indicated 
that metabolism of nicotine proceeded through hydroxylation to 5-(3'pyridyl)- 
N-methylpyrrolidine-2-o0l; oxidation to cotinine; and deamidation of cotinine 
to 4-(3'pyridyl)-4-methylamino-butyric acid. No C0» was observed (696, 699, 
700). 
After application of nicotine to mustard green, cotinine was shown to 
be the principal metabolite (577). 
Studies indicated that cotinine was the principal metabolite with 
insects also. However, the number of metabolites found varied; with tobacco 
wireworm, 1; with cigarette beetle, 2; with differential grasshopper, 4; and 
with the housefly, 3 (1281). In German and American cockroaches,too, 
cotinine was the main metabolite. In the southern armyworm, a number of 
metabolites were found but not identified (592). 
a 
The initial step in the bacterial decomposition of nicotine appeared 
to be conversion to N-methy1-3-(2 -pyrryl)pyridinium hydroxide (275). 
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